Effects of Diabetes Mellitus on Corneal Immune Cell Activation and the Development of Keratopathy.

Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45+CD11b+Ly-6G- myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1ß, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm2 in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK.

Acquired Immunostimulatory Phenotype of Migratory CD103+ Dendritic Cells Promotes Alloimmunity Following Corneal Transplantation.

Post-transplantation, T helper 1 (Th1)-mediated immune rejection is the predominant cause of graft failure. Th1 cell sensitization occurs through complex and context-dependent interaction among antigen-presenting cell subsets, particularly CD11b+ dendritic cells (DC2) and CD103+ dendritic cells (DC1). This interaction necessitates further investigation in context of transplant immunity. We use a well-established pre-clinical models of corneal transplantation and identified distinct roles of migratory CD103+ DC1 in influencing the outcomes of the grafted tissue. In recipients with uninflamed corneal beds, migratory CD103+DC1 demonstrate a tolerogenic phenotype that modulate the immunogenic capacity of CD11b+DC2 primarily mediated by IL-10, suppressing alloreactive CD4+Th1 cells via the PD-L1/PD-1 pathway, and enhancing Treg-mediated tolerance via αvß8 integrin-activated TGFß1, thus facilitating graft survival. Conversely, in recipients with inflamed and vascularized corneal beds, IFN-γ produced by CD4+Th1 cells induces migratory CD103+DC1 to adopt an immunostimulatory phenotype, characterized by the downregulation of regulatory markers including αvß8 integrin and IL-10 and the upregulation of IL-12 and costimulatory molecules CD80/86, resulting in graft failure. The adoptive transfer of ex-vivo induced tolerogenic CD103+DC1(iDC1) effectively inhibits Th1 polarization and preserves the tolerogenic phenotype of their physiological counterparts. Collectively, our findings underscore the essential role played by CD103+DC1 in modulating host alloimmune responses.

Prevalence and Determinants of Unmet Social Needs Among Rural and Urban Veterans.

PURPOSE: To examine the prevalence and determinants of nine unmet social needs among rural compared with urban Veterans. METHODS: Retrospective study using survey data collected in 2020 merged with Veterans Health Administration (VA) administrative data. For each unmet need, separate logistic regression modes were run predicting the odds of rural compared with urban Veterans endorsing the need adjusting for sociodemographic characteristics and comorbidities. FINDINGS: 2,801 Veterans responded to the survey (53.7% response rate). Veterans experienced high rates of need (e.g., 22% reported food insecurity). Unmet need prevalence varied minimally between rural and urban Veterans and where they did, rural Veterans were less likely to endorse the need (e.g., loneliness). For many unmet needs, Black compared with White Veterans were at higher risk. Regional unmet need disparities were also observed. CONCLUSIONS: As VA considers expanding unmet need interventions, tailoring interventions to the sub-populations most at risk may be warranted.

Bone Formation in a Mucinous Cystadenoma of the Ovary - Report of a Rare Case.

Bone formation in the ovary is exceedingly rare, except in the setting of dermoid cysts. Here, the author reports a case of incidental finding of heterotopic bone formation in a mucinous cystadenoma of the ovary in a 45-year-old woman who had underwent a total abdominal hysterectomy and right salpingo-oopherectomy because of hypermenorrhea during last one year with an ultrasonography report of right ovarian cyst and simultaneous multiple uterine leiomyomatas. Microscopic examination of the ovarian cyst revealed a mucinous cystadenoma with the striking finding of several thin plates of lamellar bone identified in fibrous tissue in the cyst wall. Although it is a benign finding and does not seem to have prognostic significance, it may lead to sonographic findings of concern during the evaluation of ovarian cysts.

Genome-Wide Analysis of Translation in Replicatively Aged Yeast.

Protein synthesis is an essential process that affects major cellular functions including growth, energy production, cell signaling, and enzymatic reactions. However, how it is impacted by aging and how the translation of specific proteins is changed during the aging process remain understudied. Although yeast is a widely used model for studying eukaryotic aging, analysis of age-related translational changes using ribosome profiling in this organism has been challenging due to the need for isolating large quantities of old cells. Here, we provide a detailed protocol for genome-wide analysis of protein synthesis using ribosome profiling in replicatively aged yeast. By combining genetic enrichment of old cells with the biotin affinity purification step, this method allows large-scale isolation of aged cells sufficient for generating ribosome profiling libraries. We also describe a strategy for normalization of samples using a spike-in with worm lysates that permits quantitative comparison of absolute translation levels between young and old cells.